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Acute myocarditis is an inflammatory condition that may herald the onset of dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM). We investigated the frequency and clinical consequences of DCM and ACM genetic variants in a population-based cohort of patients with acute myocarditis. This was a population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterized cardiomyopathy-associated genes with comparison to healthy controls (n=1053) sequenced on the same platform. Case ascertainment in England was assessed against national hospital admission data. The primary outcome was all-cause mortality. Variants that would be considered pathogenic if found in a patient with DCM or ACM were identified in 8% of myocarditis cases compared with

A young man presented with syncope. He was diagnosed with triglyceride deposit cardiomyovasculopathy and skeletal myopathy secondary to adipose triglyceride lipase (ATGL) deficiency. Despite optimal medical therapy, he required heart transplantation to treat his heart failure. Five years post-transplant, the graft function was normal with no evidence of triglyceride deposits. (Level of Difficulty: Intermediate.), Graphical abstract, A young man presented with syncope. He was diagnosed with triglyceride deposit cardiomyovasculopathy and skeletal myopathy secondary to adipose…

Angiogenesis 26(2), 233 - 248 (2022). doi:10.1007/s10456-022-09860-7, A wide range of cardiac symptoms have been observed in COVID-19 patients, often significantly influencing the clinical outcome. While the pathophysiology of pulmonary COVID-19 manifestation has been substantially unraveled, the underlying pathomechanisms of cardiac involvement in COVID-19 are largely unknown. In this multicentre study, we performed a comprehensive analysis of heart samples from 24 autopsies with confirmed SARS-CoV-2 infection and compared them to samples of age-matched Influenza H1N1 A (n = 16), lymphocytic non-influenza myocarditis cases (n = 8), and non-inflamed heart tissue (n = 9). We employed conventional histopathology, multiplexed immunohistochemistry (MPX), microvascular corrosion casting, scanning electron microscopy, X-ray phase-contrast tomography using synchrotron radiation, and direct multiplexed measurements of gene expression, to assess morphological and molecular changes holistically. Based on histopathology, none of the COVID-19 samples fulfilled the established diagnostic criteria of viral myocarditis. However, quantification via MPX showed a significant increase in perivascular CD11b/TIE2 + —macrophages in COVID-19 over time, which was not observed in influenza or non-SARS-CoV-2 viral myocarditis patients. Ultrastructurally, a significant increase in intussusceptive angiogenesis as well as multifocal thrombi, inapparent in conventional morphological analysis, could be demonstrated. In line with this, on a molecular level, COVID-19 hearts displayed a distinct expression pattern of genes primarily coding for factors involved in angiogenesis and epithelial-mesenchymal transition (EMT), changes not seen in any of the other patient groups. We conclude that cardiac involvement in COVID-19 is an angiocentric macrophage-driven inflammatory process, distinct from classical anti-viral inflammatory responses, and substantially underappreciated by conventional histopathologic analysis. For the first time, we have observed intussusceptive angiogenesis in cardiac tissue, which we previously identified as the linchpin of vascular remodeling in COVID-19 pneumonia, as a pathognomic sign in affected hearts. Moreover, we identified CD11b + /TIE2 + macrophages as the drivers of intussusceptive angiogenesis and set forward a putative model for the molecular regulation of vascular alterations., Published by Springer Science + Business Media B.V, Dordrecht [u.a.]

Copyright: © Katopodis et al. Severe acute respiratory syndrome (SARS) coronavirus‑2 (SARS‑CoV‑2), the causative viral agent for the ongoing COVID‑19 pandemic, enters its host cells primarily via the binding of the SARS‑CoV‑2 spike (S) proteins to the angiotensin‑converting enzyme 2 (ACE2). A number of other cell entry mediators have also been identified, including neuropilin‑1 (NRP1) and transmembrane protease serine 2 (TMPRSS2). More recently, it has been demonstrated that transmembrane protease serine 4 (TMPRSS4) along with TMPRSS2 activate the SARS‑CoV‑2 S proteins, and enhance the viral infection of human small intestinal enterocytes. To date, a systematic analysis of TMPRSS4 in health and disease is lacking. In the present study, using in silico tools, the gene expression and genetic alteration of TMPRSS4 were analysed across numerous tumours and compared to controls. The observations were also expanded to the level of the central nervous system (CNS). The findings revealed that TMPRSS4 was overexpressed in 11 types of cancer, including lung adenocarcinoma, lung squamous cell carcinoma, cervical squamous cell carcinoma, thyroid carcinoma, ovarian cancer, cancer of the rectum, pancreatic cancer, colon and stomach adenocarcinoma, uterine carcinosarcoma and uterine corpus endometrial carcinoma, whilst it was significantly downregulated in kidney carcinomas, acute myeloid leukaemia, skin cutaneous melanoma and testicular germ cell tumours. Finally, a high TMPRSS4 expression was documented in the olfactory tubercle, paraolfactory gyrus and frontal operculum, all brain regions which are associated with the sense of smell and taste. Collectively, these data suggest that TMPRSS4 may play a role in COVID‑19 symptomatology as another SARS‑CoV‑2 host cell entry mediator responsible for the tropism of this coronavirus both in the periphery and the CNS.

Although a plethora of research articles on AI methods on COVID-19 medical imaging are published, their clinical value remains unclear. We conducted the largest systematic review of the literature addressing the utility of AI in imaging for COVID-19 patient care. By keyword searches on PubMed and preprint servers throughout 2020, we identified 463 manuscripts and performed a systematic meta-analysis to assess their technical merit and clinical relevance. Our analysis evidences a significant disparity between clinical and AI communities, both in the focus on imaging modalities (AI experts neglected CT and Ultrasound, favoring X-Ray) and performed tasks (71.9% of AI papers centered on diagnosis). The vast majority of manuscripts were found deficient regarding potential use in clinical practice, but 2.7% (N=12) publications were assigned a high maturity level and are summarized in greater detail. We provide an itemized discussion of the challenges in developing clinically relevant AI solutions with recommendations and remedies., Graphical Abstract, In medical imaging, artificial intelligence (AI) has the potential to save time and cost in the healthcare system by advancing rapid patient stratification. We conducted the largest systematic review (N=463) of AI methodology on medical imaging data from COVID-19 patients. AI experts largely failed to focus on clinically relevant tasks and imaging modalities and only few publications are found valuable. On the roadmap toward developing robust and clinically valuable AI solutions, we identify key challenges and provide possible remedies.

MicroRNAs ( miRNAs) are an important class of small RNAs that regulate gene expression at the post-transcriptional level. It has become evident that miRNAs are involved in hematopoiesis, and that deregulation of miRNAs may give rise to hematopoietic malignancies. The aim of our study was to establish miRNA profiles of naive, germinal center ( GC) and memory B cells, and validate their expression patterns in normal lymphoid tissues. Quantitative (q) RT-PCR profiling revealed that several miRNAs were elevated in GC B cells, including miR-17-5p, miR-106a and miR-181b. One of the most abundant miRNAs in all three B-cell subsets analyzed was miR-150, with a more than 10-fold lower level in GC B cell as compared with the other two subsets. miRNA in situ hybridization ( ISH) in tonsil tissue sections confirmed the findings from the profiling work. Interestingly, gradual decrease of miR-17-5p, miR-106a and miR-181b staining intensity from the dark to the light zone was observed in GC. A strong cytoplasmic staining of miR-150 was observed in a minority of the centroblasts in the dark zone of the GC. Inverse staining pattern of miR-150 against c-Myb and Survivin was observed in tonsil tissue sections, suggesting possible targeting of these genes by miR-150. In line with this, the experimental induction of miR-150 lead to reduced c-Myb, Survivin and Foxp1 expression levels in the Burkitt's lymphoma cell line, DG75. In conclusion, miRNA profiles of naive, GC and memory B cells were established and validated by miRNA ISH. Within the GC cells, a marked difference was observed between the light and the dark zone. Laboratory Investigation (2009) 89, 708-716; doi:10.1038/labinvest.2009.26; published online 6 April 2009

Hypothesis Laparoscopic liver surgery is significantly limited by the technical difficulty encountered during transection of substantial liver parenchyma, with intraoperative bleeding and bile leaks. This study tested whether the use of a bioabsorble staple line reinforcement material would improve outcome during stapled laparoscopic left lateral liver resection in a porcine model.Study design A total of 20 female pigs underwent stapled laparoscopic left lateral liver resection. In group A (n = 10), the stapling devices were buttressed with a bioabsorbable staple line reinforcement material. In group B (n = 10), standard laparoscopic staplers were used. Operative data and perioperative complications were recorded. Necropsy studies and histopathological analysis were performed at 6 weeks. Data were compared between groups with the Student's t-test or the chi-square test.Results Operating time was similar in the two groups (64 +/- 11 min in group A versus 68 +/- 9 min in group B, p = ns). Intraoperative blood loss was significantly higher in group B (185 +/- 9 mL versus 25 +/- 5 mL, p Conclusion Use of a bioabsorbable staple line reinforcement material reduces intraoperative bleeding and perioperative bile leaks during stapled laparoscopic left lateral liver resection in a porcine model.

Introduction Primary diffuse large B-cell lymphomas (DLBCL) constitute a heterogeneous group of tumors with a great diversity in both clinical presentation and outcome. Besides nodal DLBCL, about 40% of these tumors present in different extranodal sites, both immune privileged sites such as the testis and the central nervous system (PCNSL) but also non immune privileged sites such as bone, stomach, skin and mediastinum. Remarkably each of these sites show a marked divergence in biological behavior. Recent studies have shown that certain non-coding short RNAs (22nt) called miRNAs may play a role in the pathogenesis of DLBCL. These miRNAs posttrancriptionally down regulate expression of genes. Aim of study To examine the expression levels of selected miRNAs in different DLBCL sites. Methods and Materials 51 cases of Ann Abour stage I and II primary DLBCL were divided into 4 groups; 19 nodal cases, 11 non-immune privileged site-associated (non-IP) extranodal cases, 9 PCNSL, and 12 testicular DLBCL. Each case was classified GCB or non-GCB using the algorithm as described by Hans et al. 13 miRNAs were selected from current literature on the basis of their involvement in B-cell lymphoma (miR-15, -16, -21, -221, -155, - 181a, -18a, -19, -20a, 17-3p, -17-5p and -92). The expression levels of the mature microRNAs were determined by qRT-PCR using Taqman miRNA assays. Results were compared by using 2−ΔCt and 2−ΔΔCt. Differences in expression levels between the four groups was tested using ANOVA. Results Of the selected microRNAs, miR-127, miR-17-5p and miR-221 show a significant difference in expression level between the immune privileged site-associated DLBCL (IP-DLBCL) and nodal DLBCL. Both miR-17-5p (p=0.0003) and miR-221 (p=0.0032) show an increased expression level in PCNSL compared to nodal DLBCL and miR-127 shows a significant increased level in testicular DLBCL compared to nodal (p=0.0011) and non-IP (p=0.0393) DLBCL. Also of interest is the fact that miR-17-5p and miR-127 show a significant difference in the level of expression between both PCNSL and testicular DLBCL. MiR-155 shows no significant difference in expression levels between nodal and extranodal DLBCL. Analysis on the basis of GCB and non-GCB classification is currently being undertaken. Conclusion In PCNSL miR-17-5p and miR-221 are specifically increased whereas miR-127 shows a specifically higher expression in testicular DLBCL when compared to non-IP and nodal DLBCL. Also PCNSL and testicular DLBCL differ in expression of miR-17-5p and miR-127. In contrast to previous reports miR-155 does not show any significant difference between nodal and extranodal groups. This may be caused by the selection of stage I or II primary DLBCL in contrast to previous publications which used a more heterogeneous group of DLBCL.